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  • Pedunculopontine stimulation from primate to patient

    19 March 2018

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinson's disease and related disorders. Here we summarise our non-human primate investigations of relevance to our surgical targeting of the PPN and relate the primate research to initial clinical experience of PPN DBS. © Springer-Verlag 2010.

  • Application of a null-beamformer to source localisation in MEG data of deep brain stimulation.

    12 December 2017

    In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG to reconstruct the neural activity of interest is challenging because of interference to the signal from the DBS device. We demonstrate that a null-beamformer can be used to localise neural activity despite artefacts caused by the presence of DBS electrodes and stimulus pulses. We subsequently verified the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray and medial prefrontal areas when the patient was in pain compared to when the patient experienced pain relief.

  • Application of a null-beamformer to source localisation in MEG data of deep brain stimulation

    3 April 2018

    In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG to reconstruct the neural activity of interest is challenging because of interference to the signal from the DBS device.We demonstrate that a null-beamformer can be used to localise neural activity despite artefacts caused by the presence of DBS electrodes and stimulus pulses. We subsequently verified the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray and medial prefrontal areas whe n the patient was in pain compared to when the patient experienced pain relief. © 2010 IEEE.

  • Deep brain stimulation for chronic pain.

    19 March 2018

    Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.

  • Deep brain stimulation

    27 October 2017

  • A specific and rapid neural signature for parental instinct.

    6 April 2018

    Darwin originally pointed out that there is something about infants which prompts adults to respond to and care for them, in order to increase individual fitness, i.e. reproductive success, via increased survivorship of one's own offspring. Lorenz proposed that it is the specific structure of the infant face that serves to elicit these parental responses, but the biological basis for this remains elusive. Here, we investigated whether adults show specific brain responses to unfamiliar infant faces compared to adult faces, where the infant and adult faces had been carefully matched across the two groups for emotional valence and arousal, as well as size and luminosity. The faces also matched closely in terms of attractiveness. Using magnetoencephalography (MEG) in adults, we found that highly specific brain activity occurred within a seventh of a second in response to unfamiliar infant faces but not to adult faces. This activity occurred in the medial orbitofrontal cortex (mOFC), an area implicated in reward behaviour, suggesting for the first time a neural basis for this vital evolutionary process. We found a peak in activity first in mOFC and then in the right fusiform face area (FFA). In mOFC the first significant peak (p<0.001) in differences in power between infant and adult faces was found at around 130 ms in the 10-15 Hz band. These early differences were not found in the FFA. In contrast, differences in power were found later, at around 165 ms, in a different band (20-25 Hz) in the right FFA, suggesting a feedback effect from mOFC. These findings provide evidence in humans of a potential brain basis for the "innate releasing mechanisms" described by Lorenz for affection and nurturing of young infants. This has potentially important clinical applications in relation to postnatal depression, and could provide opportunities for early identification of families at risk.

  • Regional cerebral perfusion differences between periventricular grey, thalamic and dual target deep brain stimulation for chronic neuropathic pain.

    13 March 2018

    Regional cerebral blood flow changes were evaluated in different subcortical brain targets following deep brain stimulation (DBS) for chronic pain. Three patients with intractable neuropathic pain were assessed; one had stimulating electrodes in the ventroposterolateral thalamic nucleus (VPL), one in the periventricular grey (PVG) area, and one had electrodes in both targets. Pain relief was achieved in all patients. Cerebral perfusion was measured by single-photon emission computed tomography to determine the effects of DBS. Comparison was made between individual scans using subtraction analysis. DBS consistently increased perfusion in the posterior subcortical region between VPL and PVG, regardless of the site of stimulation. Furthermore, thalamic and dual target DBS increased thalamic perfusion, yet PVG DBS decreased perfusion in the PVG-containing midbrain region and thalamus. Dual target stimulation decreased anterior cingulate and insular cortex perfusion. The study demonstrates regional differences in cerebral perfusion between three accepted and efficacious targets for analgesic DBS.

  • The periaqueductal grey area and the cardiovascular system.

    12 December 2017

    In this chapter, we report that blood pressure can be increased or decreased depending on whether an electrode is in ventral or dorsal PAG. We also describe that it is theoretically possible to treat orthostatic hypotension. These are exciting developments not only because they provide an example of direct translational research from animal research to humans but also because they highlight a potential for future clinical therapies. The control of essential hypertension without drugs is attractive because of the side effects of medication such as precipitation of heart failure [10]. Similarly, drug treatment of orthostatic hypotension cannot differentiate between the supine and standing positions and can therefore lead to nocturnal hypertension [22, 29]. A stimulator could be turned off at night or contain a mercury switch that reacts to posture.